T Cell Tolerance to Tumors and Cancer Immunotherapy

  • Kimberly Shafer-Weaver
  • Michael Anderson
  • Anatoli Malyguine
  • Arthur A. Hurwitz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)


It is widely recognized that the immune system plays a role in cancer progression and that some tumors are inherently immunogenic. The identification of tumor-associated antigens (TAAs) has stimulated research focused on immunotherapies to mediate the regression of established tumors. Cancer-specific immunity has traditionally been aimed at activating CD8+ cytotoxic T lymphocytes (CTLs) directed against major histocompatibility complex (MHC) class I-binding peptide epitopes. Other approaches utilize T cell adoptive therapy where autologous, tumor-specific T cells propagated in vitro are transferred back into recipients. However, these strategies have met with limited success in part due to the regulatory mechanisms of T cell tolerance, which poses a considerable challenge to cancer immunotherapy. Our laboratory utilizes the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, a murine model of prostate cancer, to study mechanisms of T cell tolerization to tumor antigens. We previously demonstrated that upon encounter with their cognate antigen in the tumor microenvironment, naïve T cell become tolerized. Our ongoing studies are testing whether provision of CD4+ T cells can enhance tumor immunity by preventing CD8+ T cell tolerance. A greater understanding of the interaction between various tumor-specific T cell subsets will facilitate the design of novel approaches to stimulate a more potent antitumor immune response.


Major Histocompatibility Complex Tumor Antigen Cancer Immunotherapy Antitumor Immune Response Tumor Immunity 


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Kimberly Shafer-Weaver
    • 1
  • Michael Anderson
    • 2
  • Anatoli Malyguine
    • 1
  • Arthur A. Hurwitz
    • 2
  1. 1.Applied and Developmental Research Support ProgramSAIC-Frederick Inc., NCI-FrederickFrederickUSA
  2. 2.Tumor Immunity and Tolerance Section, Laboratory of Molecular ImmunoregulationCancer and Inflammation Program, CCR, NIHFrederickUSA

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